Slow reacting substances of anaphylaxis (SRS-A), or leukotrienes, are naturally occurring substances which cause the constriction of smooth muscle, especially bronchial muscle. The excessive release of these substances has been found to be associated with a variety of allergic and inflammatory conditions, including immediate type hypersensitivity reactions such as asthma. Additionally, evidence obtained over the past few years has shown the presence of leukotrienes in sputum of patients wich chronic bronchitis (Turnbull, et al., Lancet II, 526 (1977)) and cystic fibrosis (Cromwell, et al., Lancet II, 164 (1981)) suggesting a role of leukotrienes in the pathology of those diseases.
Thus, compounds which inhibit the release of leukotrienes are indicated for a variety of conditions, including asthma, in which leukotrienes are a factor.
A series of 6-anilino-5,8-quinoxalinediones was prepared by Ford and Joullie, J. Het. Chem., 3, 529 (1966), including p-fluoro-, p-chloro-, p-bromo-, and p-methyl-anilino-2,3-dimethyl-5,8-quinoxalinedione; no biological activity was reported for these compounds.
This invention relates to a class of quinoxalinediones, which are useful as inhibitors of leukotriene release and for the therapy of immediate hypersensitivity reactions and conditions characterized by excessive release of leukotrienes.